Test Battery Research Articles

Sleep disturbances and psychomotor retardation in the prediction of cognitive impairments in patients with major depressive disorder

BACKGROUND Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder (MDD). Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients. We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments. We also hypothesize that anxiety symptoms, especially psychic anxiety, is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors. AIM To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode. METHODS A comprehensive neurocognitive test battery assessed executive function, attention, processing speed, and memory in 162 medication-free MDD patients and 142 matched healthy controls. The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms, and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms. Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms, as well as their interactions, on cognitive impairments. RESULTS Among the depressive symptoms, sleep disturbances were associated with poorer executive function (P = 0.004), lower processing speed (P = 0.047), and memory impairments (P < 0.001), and psychomotor retardation (PR) was associated with lower processing speed in patients with MDD (P = 0.019). Notably, PR was found to mediate the impact of sleep disturbances on the processing speed. Regarding anxiety symptoms, psychic anxiety, rather than somatic anxiety, was associated with cognitive impairments in all aspects. Sleep disturbances mediated the effect of psychic anxiety on executive function [β = -0.013, BC CI (-0.027, -0.001)] and memory [β = -0.149, BC CI (-0.237, -0.063)], while PR mediated its effect on processing speed (β = -0.023, BC CI (-0.045, -0.004)]. CONCLUSION Sleep disturbances may be a key predictor of poorer executive function, lower processing speed, and memory loss, while PR is crucial for lower processing speed during a depressive episode. Psychic anxiety contributes to all aspects of cognitive impairments, mediated by sleep disturbances and PR.

Association of glymphatic system dysfunction with cognitive impairment in temporal lobe epilepsy

ObjectivesTo explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE).MethodsThis study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF).ResultsCompared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p < 0.05) and lower values of mean DTI-ALPS index (1.491 ± 0.142 vs. 1.642 ± 0.123, p < 0.001). Significantly lower DTI-ALPS index values were observed in the ipsilateral hemisphere than in the contralateral hemisphere (1.466 ± 0.129 vs. 1.517 ± 0.175, p = 0.013) for patients with unilateral TLE. Correlation analyses found that SVF performance was significantly or borderline significantly associated with glymphatic function (FDR-corrected p < 0.05 for all DTI-ALPS index and FDR-corrected p = 0.057 for CPV) in TLE patients. Linear regression analyses showed that increased CPV and decreased DTI-ALPS index were independent risk factors for semantic fluency impairment (all p < 0.05). Furthermore, mediation analyses found the mediator role of the mean DTI-ALPS index in the relationship between choroid plexus enlargement and semantic fluency impairment (indirect effect: β = −0.182, 95%CI = −0.486 to −0.037).ConclusionThese findings reveal the important role of the DTI-ALPS index and CPV in SVF performance in unilateral TLE. Decreased DTI-ALPS index and increased CPV are the independent risk factors for semantic fluency impairment. The DTI-ALPS index may fully mediate the relationship between CP enlargement and SVF performance. These insights provide a radiological foundation for further investigations into the mechanism of the glymphatic system in TLE pathophysiology.

Diagnostic Accuracy of Neurocognitive and Executive Functions to Discriminate Women With and Without Fibromyalgia Syndrome: A Secondary Analysis.

Objective: The aim of the current study was to determine the capability of neurocognitive variables and executive functions to differentiate women with and without fibromyalgia syndrome (FMS). Methods: A secondary diagnostic accuracy analysis was conducted. A battery of neurocognitive and executive function tests (the D2 Attention test, the Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit test for mental inhibition, the Symbol Search for processing speed, and the Zoo Test for planning/decision-making) were collected in 129 women with FMS and 111 without FMS. The area under the receiver operating characteristic (ROC) curve, optimal cut-off point, sensitivity, specificity, and positive and negative likelihood ratios (LR) for each variable were calculated. Results: Between-group differences were identified in ROCF_Copy (p = 0.043), ROCF_Recall (p = 0.004), d2_TR (p = 0.019), d2_TA (p = 0.007), d2_TOT (p = 0.005), d2_CON (p = 0.004), d2_C (p = 0.042), Symbol Search (p = 0.008), Decoding _FDT (p = 0.001), Retrieving_FDT (p = 0.001), and Inhibiting_FDT (p = 0.024). The result showed that FDT-based outcomes (Retrieving_FDT: ROC 0.739, sensitivity 85.3%, specificity 48.6%; Decoding_FDT: ROC 0.724, sensitivity 50.4%, specificity 16.2%; Inhibiting_FDT: ROC 0.708, sensitivity 56.6%, specificity 22.5%) were the variables able to differentiate between women with and without FMS. Conclusions: Although women with FMS exhibited deficits in attention, long-term visual memory, processing speed, and mental inhibition when compared with women without FMS, only mental inhibition scores showed moderate diagnostic accuracy to discriminate between women with and without FMS. Future studies investigating these results in clinical settings are needed to identify the clinical relevance of these findings.

Path analysis reveals cross-country differences between Czech and Chinese university students in effect of internet and smartphone addiction, mental health, and personality traits on academic achievement in the post-pandemic era

Despite extensive evidence on the impact of various mental health issues including smartphone/internet addiction, and personality traits on academic achievement, little is known about the complex interactions between multiple of these factors simultaneously, as well as cross-country differences in these nuanced relationships. In particular, understanding the role of the mentioned addictions has become increasingly important in recent years in the context of the COVID-19 pandemic. The aim of this cross-country study was to investigate, using path analysis, the complex relationships between mental health determinants (depression, anxiety, stress, resilience, and smartphone/internet addiction) and academic achievement in 1785 Czech and Chinese university students using an online battery of psychological tests. The results confirmed the previously described effect of multiple factors (anxiety, stress, resilience, smartphone/internet addiction, personality traits, and sex, Extraversion, Agreeableness, Conscientiousness) on academic achievement, overlapping in most cases for both groups of students. At the same time, however, different country-dependent patterns of interactions emerged. For the Czech students, the variables formed a complex network of interacting factors, whereas for the Chinese students, the effect of each cluster of factors was separate for individual domains of academic achievement. These cross-country differences have implications particularly for planning and targeting the most effective interventions to promote and develop academic achievement.

Central Auditory Processing Abilities in Children with Non-Syndromic Cleft Lip and Palate: An Electrophysiological Study.

The present study compared the central auditory processing abilities using electrophysiological tests in children with non-syndromic cleft lip and palate (NSCLP) and their age-matched control group. Thirty children aged 7 to 15 years were recruited for the study. Participants were divided into 2 groups. The clinical group (children with NSCLP) comprised 15 children, while the control group (craniofacially typical peers) comprised 15 children with normal hearing sensitivity and auditory processing skills. Electrophysiological tests, including auditory brainstem responses (ABR), binaural interaction component (BIC) of ABR, auditory late latency responses (ALLR), and P300 were assessed. The results showed deviant responses in ABR, BIC, and ALLR in children with NSCLP compared to craniofacially typical counterparts. However, no significant difference was observed in P300 between the two groups. Children with NSCLP may be at a higher risk of central auditory processing disorder due to their abnormal neural transmission in the auditory nervous system. Also, assessing auditory processing abilities in children with NSCLP should include electrophysiological tests in the test battery for additional information regarding neural transmission.

Changes in Y-Balance Test Scores During Months 4, 5, and 6 of ACL Reconstruction Rehabilitation.

The anterior cruciate ligament (ACL) is well researched since injuries typically result in lengthy recoveries and rehabilitation periods until athletes can return to full activity. Although a large body of literature on the early and late stages of rehabilitation following ACL reconstructive (ACLR) surgery exists, less is known regarding the mid-phase of ACL rehabilitation and healthy versus injured limb differences in functional testing during this stage. The purpose of this study is to determine if Y-Balance Test (YBT) scores obtained during the mid-phase of ACLR rehabilitation change over months 4, 5, and 6. Case Series. Research laboratory. Patients or Other Participants: A total of 27 participants (17 females; 18.96±3.02 years (range 15-24); 173.63±10.29cm; 72.55±17.83kg) who sustained a unilateral ACL injury, experienced no episodes of instability or knee giving away, had not suffered a previous ACL injury, and expressed a desire to return to sport at the end of rehabilitation came in once a month following ACLR to participate in a battery of tests. YBT scores in the anterior, posterolateral (PL), and posteromedial (PM) directions in the healthy and reconstructed limbs. A main effect for limb was observed for the anterior (Healthy: m4: 78.8cm±5.8, m5: 79.5cm±5.2, m6: 79.4±5.8; Reconstructed: m4: 77.2±5.9, m5: 78.5±5.1, m6: 78.1±6.4, p=0.023) and PM (Healthy: m4: 80.0cm±8.7, m5: 81.0cm±9.1, m6: 82.9cm±8.9; Reconstructed: m4: 79.3cm±6.8, m5: 79.4cm±8.2, m6: 81.1cm±8.5, p=0.013). directions indicating that the reconstructed limb performed worse than the healthy limb. A main effect for time was observed for the PL direction (Healthy: m4: 78.8cm±5.8, m5: 79.5cm±5.2, m6: 79.4cm±5.8; Reconstructed: m4: 77.2cm±5.9, m5:78.5cm±5.1, m6: 78.1cm±6.4, p=0.023). The YBT measured improvement in the PL direction across time in the reconstructed limb. In the PM and anterior directions, the YBT did not measure these same improvements across this period.

Disrupted Hippocampal-Prefrontal Networks in a Rat Model of Fragile X Syndrome: A Study Linking Neural Dynamics to Autism-Like Behavioral Impairments.

FMR-KO and control rats underwent a battery of behavioral tests assessing sociability, memory, and anxiety. Single-unit electrophysiology recordings were then conducted to measure patterns of neural activity in H-PFC circuit. Advanced mathematical models were used to characterize the patterns that were then compared between groups using generalized linear mixed models. FMR-KO rats demonstrated significant behavioral deficits in sociability, spatial learning, and anxiety, aligning with symptoms of ASD. At the neural level, these rats exhibited abnormal firing patterns in the H-PFC circuit that is critical for learning, memory, and social behavior. The neural networks in FMR-KO rats were also less densely connected and more fragmented, particularly in hippocampal-PFC correlated firing. These findings suggest that disruptions in neural network dynamics underlie the observed behavioral impairments in FMR-KO rats. FMR-KO significantly disrupts several characteristics of action potential firing in the H-PFC network, leading to deficits in social behavior, memory, and anxiety, as seen in FXS. This disruption is characterized by less organized and less resilient hippocampal-PFC networks. These findings suggest that therapeutic strategies aimed at normalizing neural dynamics, such as with brain stimulation, could potentially improve behavior and cognitive functions in autistic individuals. Fragile X Syndrome is associated with autism, cognitive challenges and anxietyThe loss of Fmr1 protein disrupts processes involved in building neural networksThe consequence is abnormal neural dynamics in hippocampal-prefrontal cortex networksNormalization of dynamics could improve outcomes in FXS and ASD.

The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV.

Pre-clinical studies have demonstrated direct influences of the sympathetic and vagal/parasympathetic branches of the autonomic nervous system (ANS) on the immune system. The relevance of these pathways to the development of inflammatory disorders in humans remains unknown. We hypothesized that a comprehensive examination of the ANS-immune network in patients with HIV, would reveal that the type and severity of autonomic neuropathy (AN) would predict immune phenotypes with distinct clinical and demographic characteristics. This is a cross-sectional study of 79 adult people with a history of well-controlled HIV on stable combination antiretroviral treatment (CART) recruited from a primary care clinic network within the Mount Sinai Health System in New York City. All participants underwent a standardized battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A). Immune profiling included: 1) measurement of interleukin-6 (IL-6) as part of the Olink assay Target 96 Inflammation Panel, 2) non-negative matrix factorization (NMF) clustering analyses on Olink immune biomarkers, and 3) mass cytometry (CyTOF) on a subset of participants with and without autonomic neuropathy (N = 10). Reduced activity of caudal vagal circuitry involved in the cholinergic anti-inflammatory pathway (CAP) predicted higher levels of IL-6 (Spearman's rho = -0.352, p=0.002). The comprehensive assessment of the ANS-immune network showed four immunotypes defined by NMF analyses. A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy (AN). This association was driven by deficits in the cardiovascular sympathetic nervous system and remained strongly significant after controlling for the older age and greater burden of co-morbid illness among participants with this immunotype (aOR=4.7, p=0.017). Our results provide novel support for the clinical relevance of the CAP in patients with chronic inflammatory AN. These data also provide insight regarding the role of the sympathetic nervous system and aging in the progression and development of co-morbidities in patients with chronic HIV and support future research aimed at developing therapies focused on modulation of the sympathetic and parasympathetic/vagal nervous system.

Mapping the influence: Institutional blockholder coordination and climate change risk disclosure

This study investigates the relationship between institutional blockholder coordination, proxied by geographic proximity, and climate change risk disclosure. Using a sample of 2,887 firm-year observations for S&P 500 companies from 2010 to 2022, we reveal that a firm's climate change risk disclosure decreases when its institutional blockholders are more coordinated. In addition, we find that the negative relationship between institutional blockholder coordination and climate change risk disclosure manifests more in firms with less diversified institutional blockholders, a smaller number of institutional blockholders, a prominent position to their blockholders, and more dedicated institutional blockholder ownership. Moreover, we find that the negative association between institutional blockholder coordination and climate change risk disclosure is more pronounced in firms with corporate general counsels, a non-concentrated customer base, higher asset tangibility, and those that are environmentally sensitive. Our main conclusion still holds after using an alternative measure for climate change risk disclosure as well as a battery of endogeneity tests. Finally, we propose that institutional blockholder coordination lessens climate change risk disclosure through the channel of increased performance-induced CEO dismissal. Collectively, this study provides insightful implications for academics, financial statement users, regulators, and policymakers.

Modern alternative research methods in genetic toxicology (literature review)

The review represents the current principles of assessment of chemicals genotoxicity. The main attention is paid to alternative research methods. The international experience of the application of alternative approaches and prospects of their use for regulatory purposes are discussed. The data for this review were collected from the Russian and foreign literature, as well as Internet resources, concerning the development of the new alternative methods for testing chemicals for genotoxicity. The OECD database, Scopus, Medline, Google Scholar, RISC, CyberLeninka were used for the information retrieval. Although the evaluation of genotoxicity of chemical substances is the well-established and based on the battery of validated methods, the studies for improving the existing tests and developing new technologies, including the alternative approaches, continue unabated up to now. In general, three trends of development of genetic toxicology can be outlined, including creating of new methods based on the whole-genome sequencing and the application of genome editing technologies; implementation of quantitative system of effects assessment in addition to the existing qualitative approach (mutagenic/non-mutagenic) and testing of various combinations of genotoxicity evaluation methods to identify a battery of tests with a greater predictive activity regarding carcinogenic effects. To use the developed alternative models for regulatory purposes, it is necessary to provide convincing evidence that the data obtained are good predictors of the organism’s actual response to the effects of toxicants/genotoxicants, validation of methods, standardization, and harmonization of research protocols, and changes to the existing regulatory framework are required.

Neuropsychological outcomes following endovascular clot retrieval and intravenous thrombolysis in ischemic stroke.

Cognitive impairment, anxiety, depression, fatigue, and dependence in instrumental activities of daily living (ADL) are common after stroke; however, little is known about how these outcomes may differ following treatment with endovascular clot retrieval (ECR), intravenous tissue plasminogen activator (t-PA), or conservative management. Patients were recruited after acute treatment and invited to participate in an outcome assessment 90-120 days post-stroke. The assessment included a cognitive test battery and several questionnaires. The COVID-19 pandemic led to significant disruptions in recruitment and data collection, and the t-PA and conservative management groups were combined into a standard medical care (SMC) group. Sixty-two participants were included in the study (ECR = 31, SMC = 31). Mean age was 66.5 (20-86) years, and 35 (56.5%) participants were male. Participants treated with ECR had significantly higher National Institutes of Health Stroke Scale scores at presentation and significantly lower education. After adjusting for stroke severity, premorbid intellectual ability, and age, treatment with ECR was associated with significantly better performances on measures of cognitive screening, visual working memory, and verbal learning and memory. Participants treated with ECR also experienced less fatigue and were more likely to achieve independence in basic and instrumental ADLs. Despite this, cognitive impairment and fatigue were still common among participants treated with ECR and anxiety and depression symptoms were experienced similarly by both groups. Cognitive impairment and fatigue were less common but still prevalent following treatment with ECR. This has important practical implications for stroke rehabilitation, and routine assessment of cognition, emotion, and fatigue is recommended for all stroke survivors regardless of stroke treatment and functional outcome.

Isolated during adolescence: long-term impact on social behavior, pain sensitivity, and the oxytocin system in male and female rats

BackgroundAdolescent social isolation (ASI) has profound long-term effects on behavioral and neural development. Despite this, the specific long-term impact of ASI during different adolescent stages and across sexes remain underexplored.MethodsOur study addresses this gap by examining the effects of early- and late- adolescent social isolation on both male and female rats. Rats were either isolated (or group-housed) starting from PD 21 (early) or PD 42 (late) for three weeks and then rehoused into groups. In adulthood (PD 90), rats underwent a battery of tests: elevated plus-maze, open field, novel object recognition, social interaction and social recognition memory and hotplate tests. Finally, we analyzed oxytocin receptor binding in several regions in the brains of a second cohort of rats.ResultsBoth, male and female rats from the late adolescent social isolation (LASI) groups spent significantly less time interacting in the social interaction test. Additionally, we observed a general decrease in social recognition memory regardless of sex. Both male ASI groups demonstrated heightened thermal pain sensitivity, while the opposite was observed in early adolescent social isolation (EASI) female rats. In the brain, we observed changes in oxytocin receptor (OTR) binding in the paraventricular nucleus of the hypothalamus (PVN) and paraventricular nucleus of the thalamus (PVT) and central amygdala (CeA) with the largest changes in EASI and LASI female rats.ConclusionOur model demonstrates long-lasting alterations on behavior and oxytocin receptor binding levels following ASI providing insights into the long-term effects of ASI in a time- and sex-specific manner.

Auditory and vestibular function in mitochondrial patients harbouring the m.3243A>G variant

Abstract Hearing impairment is a frequent clinical feature in patients with mitochondrial disease harbouring the pathogenic variant, m.3243A>G. However, auditory neural dysfunction, its perceptual consequences, as well as implications for patient management are not established. Similarly, the association with vestibular impairment has not yet been explored. This case-control study investigated in 12 adults with genetically confirmed m.3243A>G adults (nine females; 45.5±16.3 years [range 18–66]; 47.1±21.5dB hearing level, dB) compared to 12 age, sex, and hearing level matched controls with sensory (cochlear-level) hearing loss (nine females; 46.6±11.8 years [range 23–59]; 47.7±25.4 hearing level, dB). Participants underwent a battery of electro-acoustic, electrophysiologic and perceptual tests which included: pure tone audiometry, otoacoustic emissions, auditory brainstem responses, auditory temporal processing measures, monaural/binaural speech perception, balance and vestibular testing, and self-reported questionnaires (dizziness, hearing disability). Our findings showed evidence of auditory neural abnormality and perceptual deficits greater than expected for cochlear pathology. Compared with matched controls with sensory hearing loss, adults with mitochondrial disease harbouring m.3243A>G had abnormal electrophysiologic responses from the VIIIth nerve and auditory brainstem (P = 0.005), an impaired capacity to encode rapidly occurring acoustic signal changes (P = 0.005), a reduced ability to localise sound sources (P = 0.028) and impaired speech perception in background noise (P = 0.008). Additionally, vestibular dysfunction (P = 0.011), greater perceived dizziness (P = 0.001) and reduced stance time (balance) (P=0.009) were also seen in participants with m.3243A>G mitochondrial disease when compared to matched counterparts. This pilot study revealed that auditory evaluation, including evoked potential responses from the auditory nerve/brainstem and speech perception in noise tests should form an important part of the management for individuals with m.3243A>G-related mitochondrial disease. Those presenting with hearing impairment and symptoms concerning balance and dizziness should undergo vestibular testing and appropriate management.

Association between working memory performance and parent and teacher ratings of working memory in 11-year-old children born preterm

ABSTRACT Working memory (WM) difficulties are often observed in children born preterm. We examined whether performance-based measures of WM components are associated with parent- and teacher-rated WM difficulties in the everyday life of children born very preterm and/or at very low birth weight (VPT/VLBW) at 11 years (n = 165). The WM components as defined in the original Baddeley’s model – phonological loop (PL), visuospatial sketchpad (VS), and central executive (CE) – were assessed with tasks from the Working Memory Test Battery for Children (WMTB-C) and the Wechsler Intelligence Scale for Children – Fourth edition (WISC-IV). Parents and teachers completed the WM subscale of the Behavioral Rating Inventory for Executive Functions (BRIEF). Measures of WM components were modestly associated with BRIEF scores, explaining 18.9% of the variance in parent-rated and 14.0% of teacher-rated WM difficulties. CE was the component most consistently associated with parent- and teacher-rated everyday WM. To conclude, our results suggest that tasks that utilize CE functions may best reflect WM outside of controlled test settings in the follow-up of VPT/VLBW children. However, performance and rating-scale measures provide unique information and are both needed to comprehensively assess WM skills.

The validity of studying healthy aging with cognitive tests measuring different constructs

A clinically useful characterization of the cognitive aging process requires the development of valid and robust behavioral tests, with an emphasis on explaining and understanding typical inter-individual variability in cognition. Here, using a dataset that includes behavioral scores collected with the National Institute of Health Toolbox Cognition Battery (NIHTB-CB) and other auxiliary tests, we examined (1) the differences between young and old adults across different cognitive domains, (2) the strength of across-subject correlations in behavioral test scores, (3) the consistency of low-dimensional behavioral representations across age using factor analysis, and (4) the accuracy of behavioral scores in predicting participants’ age. Our results revealed that (1) elderly females had better verbal episodic memory scores than elderly males, (2) across-subject correlations between behavioral tests varied with age group, (3) although a three-factor model explained the behavioral data in both age groups, some tasks loaded to different factors between the two groups, and (4) age-performance relationship (i.e. a regression model linking age to cognitive scores) in one group cannot be extrapolated to predict age in the other group, indicating an inconsistency in age-performance relationships across groups. These findings suggest that executive function tests might tap into different cognitive processes in different age groups, which might ultimately suggest that a statistically significant between-group difference in test performance might not always reflect differences in the same underlying cognitive processes. Overall, this study calls for more caution when interpreting age-related differences and similarities between age groups with different cognitive abilities even when the same tests are used.

Determining whether false positive rates increase with performance validity test battery expansion

Objective Performance validity test (PVT) misclassification is an important concern for neuropsychologists. The present study determined whether expanding PVT analysis from 4-PVTs to 8-PVTs could lead to elevated rates of false positive performance validity misclassifications. Method Retrospective analysis of 443 patients who underwent a fixed neuropsychological test battery in a mixed clinical and forensic setting. Rates of failing two PVTs were compared to those predicted by Monte Carlo simulations when PVT analysis extended from 4-PVTs to 8-PVTs. Indeterminate performers (IDT; n = 42; those who failed two PVTs only after PVT analysis extended from 4-PVTs to 8-PVTs) were compared to a PVT-Fail group (n = 148; those who failed two PVTs in the 4-PVT battery or failed >2 PVTs). Results Rate of failing two PVTs remained stable when PVT analysis extended from 4- to 8-PVTs (12.9 to 11.9%) and was significantly lower than those predicted by Monte Carlo simulations. Compared to PVT-Fail, the IDT group was significantly younger, had stronger neuropsychological test performance, and demonstrated comparable rates of forensic referral and conditions with known neurocognitive sequelae (e.g. stroke, moderate-to-severe TBI). Conclusions Monte Carlo simulations significantly overestimated rates of individuals failing two PVTs as PVT battery length doubled. IDT did not differ from PVT-Fail across variables with known PVT effects (e.g. age, referral context, neurologic diagnoses), lowering concern that this group is comprised entirely of false-positive PVT classifications. More research is needed to determine the effect of PVT battery length on validity classification accuracy.

Cognitive effects, pharmacokinetics, and safety of zuranolone administered alone or with alprazolam or ethanol in healthy adults in a phase 1 trial.

Zuranolone is an oral, once-daily, 14-day treatment course approved for adults with postpartum depression in the United States. To assess cognitive effects, pharmacokinetics, and safety of zuranolone, alone or with alprazolam/ethanol. This was a phase 1, two-part, two-period, randomized, double-blind, placebo-controlled crossover trial. Participants received zuranolone 50 mg or placebo once daily for 9 days, and additionally received alprazolam (1 mg, Part A), ethanol (males: 0.7 g/kg; females: 0.6 g/kg, Part B), or corresponding placebo on days 1, 5, and 9. Within each part, participants received all treatment combinations. Cognition was assessed using a computerized test battery; pharmacokinetics and safety were also evaluated. All participants (Part A, N = 24; Part B, N = 25) received ⩾1 dose of zuranolone/placebo. Compared to placebo, zuranolone produced small-to-moderate cognitive decline (Cohen's |d| = 0.126-0.76); effects were larger with alprazolam (Cohen's |d| = 0.523-0.93) and ethanol (Cohen's |d| = 0.345-0.88). Zuranolone coadministration with alprazolam (Cohen's |d| = 0.6-1.227) or ethanol (Cohen's |d| = 0.054-0.5) generally worsened cognitive decline when compared with zuranolone alone. Maximal pharmacodynamic effects occurred at approximately 5 h and were resolved by 12 h postbaseline. No pharmacokinetic interactions were observed. Incidence of adverse events was similar between groups; most events were mild or moderate in severity. A general small-to-moderate magnitude decline in cognition occurred with zuranolone alone. Coadministration with alprazolam/ethanol increased the magnitude, but not the duration, of effects compared with single-agent administration. Zuranolone prescribers and patients should be aware of the potential for increased central nervous system-depressant effects if coadministered with GABAergic active compounds such as alprazolam and ethanol.

Surgical treatment of meningiomas improves neurocognitive functioning and quality of life – a prospective single-center study

Background and purposeEarly diagnosis and the refinement of treatment of patients with intracranial meningiomas have brought quality of life (QoL) and neurocognitive functioning as outcome measures into focus. The aim of this study is a comprehensive assessment of neurocognitive function, quality of life and the presence of depression in meningioma patients before and after surgery.MethodsPatients with MRI diagnosis of intracranial meningioma and indication for surgery were prospectively included. A clinical neuropsychologist performed neurocognitive assessments within 3 months before and 12 months after surgery. The test battery included investigation of selective and divided attention, verbal and figural memory, executive functioning, and word fluency. Self-report questionnaires to assess depressive symptoms, QoL, and disease coping were administered. Raw values and t-values were compared pre-and postoperatively. Outcome was stratified by tumor- and peritumoral brain edema (PTBE) volumes, postoperative resolution of PTBE and WHO grade. The study included 18 predominantly female patients (83%) with a median age of 59 years and mostly CNS WHO grade 1 meningiomas (83%).ResultsThere was a significant postoperative improvement in the ability to selectively react under stress, in working memory and improved delayed reproduction of verbal and visual memory content. QoL improved regarding a reduction in physical problems, an improvement in energy, and social functioning. There was a trend towards worse preoperative scores in all tests, and greater postoperative improvement in patients with PTBE. Tumor volume had no effect on the measured outcome. The patients did not suffer from depressive symptoms before the surgery but improved postoperatively and most patients had an active, problem-oriented coping strategy.ConclusionResection of intracranial meningiomas leads to an improvement in multiple neurocognitive domains and QoL. There is a trend towards poorer preoperative neurocognitive functioning and greater postoperative improvement in patients with PTBE. Depression appears to play a minor role in the context of neurocognitive functioning and disease coping.

Cognition in (pre)symptomatic Dutch-type hereditary and sporadic cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited. We included Dutch-type hereditary CAA (D-CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age-matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI-cSVD burden and cognition. D-CAA ICH- mutation carriers exhibited poorer global cognition and executive function compared to age-matched controls. Patients with sCAA performed worse across all cognitive domains compared to D-CAA ICH+ mutation carriers and age-matched controls. MRI-cSVD burden is associated with decreased processing speed. CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI-cSVD burden being associated with slower processing speed. Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH). Presymptomatic Dutch-type CAA (D-CAA) mutation carriers show worse cognition than age-matched controls. More early awareness of cognitive dysfunction in CAA before first sICH is needed. Increased cerebral small vessel disease CAA-burden on magnetic resonance imaging is linked to a decrease in processing speed.

Health-Related Field-Based Fitness Tests: Normative Values for Italian Primary School Children.

Background/Objectives: conducting fitness tests in educational settings can lead to advantages for both individuals and groups, beyond just enhancing fitness. With the aim of appropriately interpreting performance, this study was conducted to establish sex- and age-specific percentile normative data for a physical fitness (PF) protocol and to define a compound measure of physical performance. Methods: In this cross-sectional study, a short, feasible, and easy-to-administer test battery was performed for 5106 school children, aged 6-10 years. Gender- and age-specific percentiles for the PF tests were constructed, and a Physical Fitness-Motor Competence Performance Index (PF-MC PI) was calculated according to the percentiles. Results: Boys scored higher in all the PF tests when compared to girls (p < 0.001). There was also a trend towards increased PF levels as the age increased in both genders (p < 0.0001). Correlations between scores on individual test items were moderate to high (r from 0.549 to 0.700), and all individual test item scores significantly correlated with the PF-MC PI (p < 0.0001). Conclusions: the provided percentile values will enable the correct interpretation and monitoring of the fitness status of children and the PF-MC PI can be used for easily rating children's health-related fitness qualities.